title: Volumetric characterization of sodium-induced G-quadruplex formation.
abstract: Oligodeoxyribonucleotides (ODN) with repeats of the human telomeric sequence can adopt different tetrahelical conformations that exhibit similar energetic parameters. We studied the volumetric properties of the folded and unfolded states of an ODN with four repeats of the human telomeric sequence, d[A(GGGTTA)(3)GGG], by combining pressure-perturbation calorimetry (PPC), vibrating tube densimetry, ultrasonic velocimetry, and UV melting under high pressure. We carried out our volumetric measurements in aqueous buffers at pH 7 containing 20, 50, and 100 mM NaCl. All of the methods employed yielded volumetric parameters that were in excellent agreement. The molar volume changes, ΔV, of the conformational transition leading to formation of the folded state are large and positive. At 50 mM NaCl, the average transition volume, ΔV(tr), obtained from all the methods is 56.4 ± 3.5 cm(3) mol(-1) at the transition temperature of 47 °C, with ΔV(tr) decreasing with an increase in temperature. We carried out a molecular dynamics simulation of the change in the intrinsic geometric parameters of the ODN accompanying quadruplex formation. On the basis of the experimental and computational results, the folding transition of the ODN is accompanied by a release of 103 ± 44 water molecules from its hydration shell to the bulk. This number corresponds to ~18% of the net hydration of the coil conformation.
authors.affiliation: Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, Ontario M5S 3M2, Canada.
authors.forename: Helen Y
authors.initials: HY
authors.lastname: Fan
authors.forename: Yuen Lai
authors.initials: YL
authors.lastname: Shek
authors.forename: Amir
authors.initials: A
authors.lastname: Amiri
authors.forename: David N
authors.initials: DN
authors.lastname: Dubins
authors.forename: Heiko
authors.initials: H
authors.lastname: Heerklotz
authors.forename: Robert B
authors.initials: RB
authors.lastname: Macgregor
authors.forename: Tigran V
authors.initials: TV
authors.lastname: Chalikian
mesh_terms: D004563:Electrochemistry; D054856:G-Quadruplexes; D006801:Humans; D008958:Models, Molecular; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D012965:Sodium Chloride / Q000737:chemistry*
chemical_list: D009838:Oligodeoxyribonucleotides; D012965:Sodium Chloride